新产品编号:922815
Chemical Name: N-(4-Bromobenzylsulfonyl)-D-seryl-N1-(4-guanidinobenzyl)-L-alaninamide
CAS No. 400721-44-0
项目整合开发状态: Biological Testing
项目研究机构: Corvas (Originator)
合成路线:4-Nitrobenzylamine (I) is protected as the corresponding trifluoroacetamide (II) and subsequently reduced to aniline (III) by catalytic hydrogenation over Pd/C.Condensation of (III) with N,N'-di-Boc-N''-(trifluoromethanesulfonyl)guanidine (IV) furnishes the Boc-protected guanidine (V).The trifluoroacetamide function of (V) is then hydrolyzed by means of K2CO3 in aqueous MeOH to provide amine (VI).(1,2)
合成路线:Acylation of O-t-butyl-D-serine methyl ester (VII) with sulfonyl chloride (VIII) yields sulfonamide (IX).After saponification of the methyl ester group of (IX) employing LiOH,the resultant carboxylic acid (X) is coupled to L-alanine t-butyl ester (XI) to furnish the sulfonyl dipeptide (XII).Acidic cleavage of the t-butyl ester group of (XII) gives rise to the carboxylic acid (XIII).This is then coupled to the benzylic amine (VI) to afford amide (XIV).Finally,the N-Boc protecting groups of (XIV) are removed by treatment with trifluoroacetic acid in CH2Cl2.(1,2)
📌 参考资料/链接：
参考文献标题:Non-covalent inhibitors of urokinase and blood vessel formation
文献作者:Semple,J.E.; Levy,O.E.; Tamiz,A.P.; Madison,E.L.; Weinhouse,M.I.(Corvas International,Inc.)
参考来源:EP 1182207; WO 0214349
📄 详细内容
合成路线:4-Nitrobenzylamine (I) is protected as the corresponding trifluoroacetamide (II) and subsequently reduced to aniline (III) by catalytic hydrogenation over Pd/C.Condensation of (III) with N,N'-di-Boc-N''-(trifluoromethanesulfonyl)guanidine (IV) furnishes the Boc-protected guanidine (V).The trifluoroacetamide function of (V) is then hydrolyzed by means of K2CO3 in aqueous MeOH to provide amine (VI).(1,2)
合成路线:Acylation of O-t-butyl-D-serine methyl ester (VII) with sulfonyl chloride (VIII) yields sulfonamide (IX).After saponification of the methyl ester group of (IX) employing LiOH,the resultant carboxylic acid (X) is coupled to L-alanine t-butyl ester (XI) to furnish the sulfonyl dipeptide (XII).Acidic cleavage of the t-butyl ester group of (XII) gives rise to the carboxylic acid (XIII).This is then coupled to the benzylic amine (VI) to afford amide (XIV).Finally,the N-Boc protecting groups of (XIV) are removed by treatment with trifluoroacetic acid in CH2Cl2.(1,2)
参考文献标题:Synthesis and biological activity of non-transition state urokinase inhibitors
文献作者:Tamiz,A.P.; Weinhouse,M.I.; Ahn,J.S.; Alfaro-Lopez,J.; Gaudette,J.; Meneses,J.K.; Roberts,C.; Madison,E.L.; Semple,J.E.; Levy,O.E..
参考来源:28th Natl Med Chem Symp (June 8 2002,San Diego) 2002,Abst 59